EMC1 Is Required for the Sarcoplasmic Reticulum and Mitochondrial Functions in the <i>Drosophila</i> Muscle
Carlos Antonio Couto-Lima,
Maiaro Cabral Rosa Machado,
Lucas Anhezini,
Marcos Túlio Oliveira,
Roberto Augusto da Silva Molina,
Rodrigo Ribeiro da Silva,
Gabriel Sarti Lopes,
Vitor Trinca,
David Fernando Colón,
Pablo M. Peixoto,
Nadia Monesi,
Luciane Carla Alberici,
Ricardo Guelerman P. Ramos,
Enilza Maria Espreafico
Affiliations
Carlos Antonio Couto-Lima
Department of Cell and Molecular Biology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil
Maiaro Cabral Rosa Machado
Department of Cell and Molecular Biology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil
Lucas Anhezini
Cellular and Molecular Biology Program, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil
Marcos Túlio Oliveira
Department of Biotechnology, College of Agricultural and Veterinary Sciences, Sao Paulo State University, Jaboticabal 14884-900, SP, Brazil
Roberto Augusto da Silva Molina
Department of Cell and Molecular Biology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil
Rodrigo Ribeiro da Silva
Department of Cell and Molecular Biology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil
Gabriel Sarti Lopes
Department of Cell and Molecular Biology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil
Vitor Trinca
Cellular and Molecular Biology Program, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil
David Fernando Colón
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil
Pablo M. Peixoto
Baruch College and Graduate Center, The City University of New York, New York, NY 10010, USA
Nadia Monesi
Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-903, SP, Brazil
Luciane Carla Alberici
Department of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil
Ricardo Guelerman P. Ramos
Department of Cell and Molecular Biology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil
Enilza Maria Espreafico
Department of Cell and Molecular Biology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, SP, Brazil
EMC1 is part of the endoplasmic reticulum (ER) membrane protein complex, whose functions include the insertion of transmembrane proteins into the ER membrane, ER–mitochondria contact, and lipid exchange. Here, we show that the Drosophila melanogaster EMC1 gene is expressed in the somatic musculature and the protein localizes to the sarcoplasmic reticulum (SR) network. Muscle-specific EMC1 RNAi led to severe motility defects and partial late pupae/early adulthood lethality, phenotypes that are rescued by co-expression with an EMC1 transgene. Motility impairment in EMC1-depleted flies was associated with aberrations in muscle morphology in embryos, larvae, and adults, including tortuous and misaligned fibers with reduced size and weakness. They were also associated with an altered SR network, cytosolic calcium overload, and mitochondrial dysfunction and dysmorphology that impaired membrane potential and oxidative phosphorylation capacity. Genes coding for ER stress sensors, mitochondrial biogenesis/dynamics, and other EMC components showed altered expression and were mostly rescued by the EMC1 transgene expression. In conclusion, EMC1 is required for the SR network’s mitochondrial integrity and influences underlying programs involved in the regulation of muscle mass and shape. We believe our data can contribute to the biology of human diseases caused by EMC1 mutations.